Chapter 7: How We Study the Brain's Structures and Functions Flashcards
who argued that language functions are located in the brain’s frontal lobes at the Anthropological Society of Paris 1861?
Ernest Auburtin
who observed a brain-injured patient who lost his speech + only said “tan”, then soon died; injury was found in the ___
Paul Broca; left frontal lobe
Broca’s area
third frontal convolution of the left frontal lobe
study of the relationships between brain function + behaviour, especially in human
neuropsychology
today, measuring brain + behaviour includes:
- noninvasive imaging
- complex neuroanatomical measurement
- sophisticated behavioural analyses
scientists can stain sections of brain tissue to identify ___ viewed with a light microscope (low magnification)
cell bodies
scientists can selectively stain individual neurons to reveal ___ with a light microscope (high magnification)
their complete structure
an electron microscope makes it possible to view ___ in detail
synapses
multiphoton imaging can generate a 3D image of ___
living tissue
who was able to use light microscopic techniques to divide the cerebral cortex into many distinct zones based on the characteristics of neurons in those zones?
Korbinian Brodmann
___ is being used to identify the locations of different receptors on the membranes of cells
super-resolution microscopy
who developed a transgenic technique that involves labelling different neurons by highlighting them with distinct colours (Brainbow)
Jean Livet
what structure do mammals require for remembering the context in which they encounter information?
dentate gyrus (subregion of hippocampus)
preventing the growth of new ___ leads to certain kinds of memory deficits
dentate gyrus neurons
___ is important in protein + carbohydrate metabolism
corticosterone, a hormone secreted in times of stress
when rats have their adrenal glands removed, it eliminates the hormone ___. without this, neurons in the ___ die
corticosterone; dentate gyrus
what was the conclusion of the experiment with ADX rats?
dentate gyrus neurons are necessary for contextual learning
study of the biological bases of behaviour in humans + other animals
behavioural neuroscience
a major challenge for behavioural neuroscientists
developing methods for studying both typical & atypical behaviour
measuring behaviour in humans & lab animals differs in large part because ___
humans speak (can ask about symptoms)
the objective study of animal behaviour, especially under natural conditions, which provided the basis for modern behavioural neuroscience
ethology
3 neuropsychological tests regarding memory
- Corsi block-tapping test
- mirror-drawing task
- test of recent memory
the examiner taps out a sequence of blocks, the block numbers are visible on the examiner’s side of the board but not on the participant’s
Corsi block-tapping test
participants’ task is to trace between the 2 outlines of the star while looking only at their hand in a mirror, crossing a line constitutes an error
mirror-drawing task
participants’ task is to identify which picture they saw most recently
test of recent memory
___ have very large behavioural repertoires, meaning they display a long list of capabilities
rats
the rat must find the platform from a # of different starting locations in the pool, the only cues available are outside the pool (in the room)
place learning
the rat has already learned that a platform always lies somewhere in the pool, but the rat enters the pool from a different starting location each day
matching-to-place learning
the rat must find the platform from a cue on the pool wall
landmark
a major problem facing people with stroke is a ___
deficit in controlling hand/limb movements
who developed an automated touchscreen platform for cognitive/motivational testing of rodents?
Tim Bussey + Lisa Saksida
2 reasons to manipulate the brain to see how behaviour changes
- develop hypotheses abt how the brain affects behaviour
- develop animal models of neurological/psychiatric disorders
brain manipulation techniques
inactivate the brain via
- lesions
- drugs
activate it via
- electrical stimulation
- drugs
- light
the first + simplest technique used for brain manipulation
ablate (remove/destroy) tissue
who used ablation in the 1920s to find the site of memory in the brain
Karl Lashley
who trained monkeys and rats on various mazes and motor tasks and then removed bits of cerebral cortex, with the goal of producing amnesia for specific memories
Karl Lashley
Lashley observed that memory loss was related to ___, and that memory is ___
the amount of tissue he removed; distributed throughout the brain, not in any single place
who removed both hippocampi as a treatment for epilepsy?
William Scoville and Brenda Milner
why did Lashley never remove the hippocampi?
he had no reason to believe the structures had any role in memory
surgical instrument that permits a researcher or neurosurgeon to target a specific part of the brain
stereotaxic apparatus
rostral-caudal measurements correspond to the ___
y-axis
dorsal-ventral measurements correspond to the ___
z-axis
medial-lateral measurements correspond to the ___
x-axis
high-intensity focused ultrasound (HIFU) is used to help treat ___ as opposed to invasive neurosurgery
Parkinsonian tremor
how does high-intensity focused ultrasound (HIFU) work?
beams heat tissue
following brain damage, the neuroplastic ability to modify behaviour from that used prior to damage
compensation
to avoid compensation following permanent lesions, researchers have also developed temporary + reversible lesion techniques such as ___
regional cooling, which prevents synaptic transmission
how does regional cooling work?
- hollow metal coil placed next to a neural structure, then chilled fluid is passed thru the coil, cooling the brain structure to 18C
- when chilled fluid removed from coil, brain structure quickly warms & synaptic transmission is restored
why is it possible to selectively turn brain regions on/off?
the brain operates on both electrical and chemical energy
who was the first to use electrical stimulation directly on the human cerebral cortex during neurosurgery?
Wilder Penfield
___ is when animals have the opportunity to press a bar to turn on a current to their lateral hypothalamus, which triggers them to eat
electrical self-stimulation
___ affects a neural circuit that involves both eating and pleasure
electrical self-stimulation
when the intact cortex adjacent to cortex injured by a stroke is stimulated electrically leads to
improvement in motor behaviours
who successfully restored motor deficits in a rat model of Parkinson disease by electrically stimulating a specific brain nucleus?
Cam Teskey
neurosurgery in which electrodes implanted in the brain stimulate a targeted area w/ a low-voltage electrical current to produce/facilitate behaviour
deep-brain stimulation (DBS)
in Parkinson patients, DBS to the ___ makes movements smoother, often allowing patients to dramatically reduced their intake of medications
globus pallidus in the basal ganglia
___ of the brain is invasive; holes must be drilled into the skull and an electrode lowered into the brain
electrical stimulation
procedure in which a magnetic coil is placed over the skull to stimulate the underlying brain; used either to induce behaviour or to disrupt ongoing behaviour
transcranial magnetic stimulation (TMS)
in TMS, when the motor cortex is stimulated, movement is ___, or if movement is in progress, it is ___. Similarly, if the visual cortex is stimulated, the participant sees ___
evoked; disrupted; dots of light (phosphenes)
the drug haloperidol, used to treat schizophrenia, reduces ___ function and makes healthy rats ___
dopaminergic neuron; dopey and inactive (hypokinetic)
drugs that increase dopaminergic activity, such as amphetamine, produce ___ rats
hyperkinetic
exposure to psychomotor stimulants such as amphetamine, cocaine, and nicotine can produce long-term effects on ___
the brain’s later placticity
who found that earlier nicotine-enhanced motor learning impaired later motor learning in rats?
Claudia Gonzalez
design + construction of biological devices, systems, and machines not found in nature
synthetic biology
CRISPR-Cas9 serves as an all-purpose tool for ___
cutting the DNA of any cell
the potential impact of CRISPR
- eliminate inherited diseases
- counter antibiotic-resistant microbes
- disable parasites
- improve food security
transgenic technique that combines genetics + light to excite/inhibit targeted cells in living tissue
optogenetics
optogenetics is based on the discovery that ___
light can activate certain proteins that occur naturally + have been inserted into cells of model organisms
the first opsin used for the optogenetic technique
channelrhodopsin-2 (ChR2)
when channelrhodopsin (ChR2) is exposed to ___ light, the sodium ion channel opens and immediately depolarizes the neuron, causing ___
blue; excitation
stimulation of halorhodopsin (NpHR) with a ___ light activates a ___ pump, hyperpolarizing the neuron and causing ___
green-yellow; chloride; inhibition
researches hail optogenetics for its ___
high spatial + temporal resolution
transgenic technique that combines genetics + synthetic drugs to activate targeted cells in living tissue
chemogenetics
DREADD (designer receptor exclusively activated by designer drugs) principal advantage:
the drug activates only the genetically modified receptors, and the receptors are only activated by the designer drug, not by endogenous molecules
in ___, temporal resolution is much lower than w/ optogenetics because receptors are activated by drugs rather than by light
DREADD
4 techniques for tracking the brain’s electrical activity
- single-cell recording
- electroencephalography (EEG)
- event-related potentials (ERPs)
- magnetoencephalography (MEG)
microelectrodes can be placed next to cells (___), or inside cells (___)
extracellular recording; intracellular recording
modern extracellular recording techniques make it possible to distinguish the activity of as many as ___ neurons at once
40
___ allows direct study/recording of a single neuron’s electrical activity
intracellular recording
2 disadvantages of intracellular recording
- can kill the cell
- cannot be done in awake, freely moving animals
who showed that neurons in the rat + mouse hippocampus vigorously fire when an animal is in a specific place in the environment?
John O’Keefe
hippocampal neurons maximally responsive to specific locations in the world
place cells
the 2014 Nobel Prize in Physiology or Medicine was awarded to ___ “for their discoveries of cells that constitute a positioning system in the brain.”
John O’Keefe
May-Britt Moser
Edvard I. Moser
in mice with a genetically engineered mutation that produces deficits in spatial memory, place cells lack ___ as they fire to a ___
specificity; very broad region of their world
who discovered in the 1930s that the brain’s electrical activity could be recorded simply by placing electrodes on the scalp, creating “brain waves” (EEG)?
Hans Berger
graded potentials recorded w/ electrodes placed directly on the surface of the brain (cerebral cortex)
electrocorticography (ECoG)
EEGs reveal remarkable features of the brain’s electrical activity, such as:
- behaviour changes
- the cortex displays an array of patterns, some rhythmical
- the living brain’s electrical activity is never silent, even when a person is asleep or comatose
a recorded brain wave’s height
amplitude
the # of brain waves recorded per second
frequency
when a person is aroused, excited, or alert, the EEG pattern has a ___ amplitude and a ___ frequency
low; fast
when a person is calm and relaxed, especially with eyes closed, ___ brain waves often emerge, which are called ___
rhythmical; alpha rhythms
large, extremely regular brain waves w/ a frequency ranging from 7-11 Hz; found in most people when they are relaxed w/ eyes closed
alpha rhythms
in humans, alpha rhythms are generated in the region of the ___
visual cortex at the back of the brain
if a relaxed person ___, the alpha rhythms abruptly stop
- is disturbed
- performs mental arithmetic
- opens their eyes
only in ___ does the EEG permanently become a flat line
brain death
EEG is a reliable tool for:
- monitoring sleep stages
- estimating depth of anesthesia
- evaluating the severity of head injury
- searching for brain abnormalities
brief periods of impaired awareness/unresponsiveness + involuntary movements associated w/ spiking patterns in the EEG characterize ___
electrographic seizures
complex electroencephalographic waveform related in time to a specific sensory event
event-related potentials
___ are largely the graded potentials on dendrites that a sensory stimulus triggers
ERPs
one way to detect ERPs
produce the stimulus repeatedly + average the recorded responses
2 advantages for using ERPs to study the brain
- noninvasive: electrodes are placed on the scalp, not the brain
- cost
ERPs can not only detect which brain areas are processing particular stimuli but can also be used to study ___
the order in which different regions participate (route)
P3 is a hot spot for processing ___
visual stimulus
ERPs can help reveal which brain areas are most sensitive to ___ & are most closely related to ___
aging; declining behavioural functions among the elderly
neural activity, by generating an electrical field, also produces a ___
magnetic field
magnetic potentials recorded from detectors placed outside the skull
magnetocephalogram
why can MEG yield a higher resolution than an ERP?
magnetic waves conducted thru living tissue undergo less distortion than electrical signals
major advantage of MEG over EEG/ERP
ability to more precisely identify the source of the activity of being recorded
major disadvantage of MEG
high cost
until the early 1970s, the only way to image the living brain was by using ___ to produce ___
x-rays; static images of brain anatomy from one angle
who developed the computed tomography (CT scan)?
Allan Cormack + Godfrey Hounsfield
x-ray technique that produces a static 3D image of the brain in cross-section
computed tomography (CT scan)
how does a CT work?
- x-ray passed thru object at many angles, creating many images
- images combined to make 3D image
the CT method resembles the way our ___ work to perceive ___
two eyes; depth/distance to locate an object in space
___ tissue, such as bone, absorbs lots of radiation
high-density
___ material, such as ventricular fluid or blood, absorbs little radiation
low-density
in CT, dark colours indicate ___ and light colours indicate ___
low-density regions; high-density regions
the inability to speak fluently despite having average comprehension/intact vocal mechanisms
Broca aphasia
CT has a resolution appropriate for localizing ___
brain tumors + lesions
technique that produces a static 3D brain image by passing a strong magnetic field thru the brain, followed by a radio wave, then measuring a radiofrequency signal emitted from hydrogen atoms
magnetic resonance imagine (MRI)
MRI is based on the principle that ___
hydrogen atoms behave like spinning bar magnets in the presence of a magnetic field
normally, hydrogen atoms point randomly in different directions, but when placed in a large static magnetic field, they ___
line up in parallel
in an MRI scanner, radio pulses are applied to a brain whose atoms have been aligned, and each radio pulse forms a ___, which causes ___
second magnetic field; the spinning atoms to deviate from the parallel orientation to a new orientation
in MRIs, areas with ___ stand out from areas with ___
high water content (cell body-rich areas); low water content (axon-rich areas)
in an MRI, as each radio pulse ends & the hydrogens realign w/ the static field, they ___ and a ___ detects this realignment
emit a tiny amt of energy; coil
in an MRI, based on the signals from the coil, a computer ___, producing a magnetic resonance image
re-creates the position of the hydrogen nuclei
magnetic resonance imaging method that can imagine fiber pathways in the brain by detecting the directional movements of water molecules
diffusion tensor imaging (DTI)
DTI easily detects abnormalities such as those that occur in ___
- multiple sclerosis
- stroke
- concussion
- the imaged fiber pathways & their myelin sheaths
magnetic resonance imaging method that uses the hydrogen proto signal to determine the concentration of brain metabolites; used to identify changes in specific markers of neuronal function, which is promising for accurate diagnosis of traumatic brain injuries
magnetic resonance spectroscopy (MRS)
MRS is an MRI method that uses hydrogen proton signal to determine the ___ in brain tissue
concentration of brain metabolites like N-acetylaspartate (NAA)
MRS is useful for detecting abnormalities in brain metabolism in disorders such as ___
concussion
when a brain region is active, the amt of ___ flowing to the region increases
blood, oxygen, glucose
3 functional brain imaging techniques
- functional MRI
- optical tomography
- positron emission tomography
as neurons become active, they use more oxygen, resulting in a ___
temporary dip in the blood oxygen level
active neurons increase ___ levels, which signal blood vessels to ___, ___ blood flow and bringing more ___ to the area
blood carbon dioxide; dilate; increasing; oxygen
who discovered that when human brain activity increases, the extra oxygen produced by increased blood flow actually exceeds the tissues needs = amt of oxygen in an activated brain area increases?
Peter Fox
oxygen is carried on the ___
hemoglobin molecule in red blood cells
changes in the ratio of oxygen-rich hemoglobin to oxygen-poor hemoglobin alters the blood’s magnetic properties because ___
oxygen-rich hemoglobin is less magnetic than oxygen-poor hemoglobin
in 1990, ___ showed that MRI could accurately match the changes in magnetic properties to specific brain locations (fMRI)
Segi Ogawa
magnetic resonance imaging technique that measures brain activity indirectly by detecting changes associated w/ blood flow; often used to measure cerebral blood flow during cognitive testing or resting
functional magnetic resonance imaging (fMRI)
functional changes in the brain are inferred from increases/decreases in the MRI signal produced by ___
changes in oxygen levels
the ___ resolution of fMRI is not as precise as that obtained w/ EEG or ERPs
temporal
why does fMRI offer good spatial resolution of the brain’s activity source?
dense blood vessel supply to the cerebral cortex
2 disadvantages of fMRI
- subjects must lie motionless in a long, noisy tube = claustrophobic
- confined space/lack of mobility restrict the types of behavioural experiments that can be performed
magnetic resonance imaging method that measures changes in oxygen when the individual is resting (not engaged in a specific task)
resting-state fMRI (rs-fMRI)
although rs-fMRI is still growing, we have already identified many consistent networks of brain activity/abnormalities in disease states such as ___ where patients have trouble with ___
dementia + schizophrenia; performing cognitive tasks
a functional imaging technique that operates on the principle that an object can be reconstructed by gathering light transmitted through it
optical tomography
fNIRS is a form of ___, which can image ___ like the brain
optical tomography; soft body tissue
in fNIRS, reflected infrared light is used to determine blood flow because oxygen-rich hemoglobin & oxygen-poor hemoglobin differ in their ___
absorption spectra
___ measure essentially the same thing with different tools
fNIRS and fMRI
fNIRS
advantage of fNIRS
relatively easy to hook up subjects repeatedly & record them for short periods
disadvantage to fNIRS
light does not penetrate far into the brain, so researchers are restricted to measuring cortical activity
fNIRS has been used to differentiate ___
cancerous from noncancerous brain tissue
imaging technique that detects changes in blood flow by measuring changes in the uptake of compounds such as oxygen or glucose; used to analyze the metabolic activity of neurons
positron emission tomography (PET)
what imaging method is used to study the metabolic activity of brain cells engaged in processing brain functions such as language?
positron emission tomography (PET)
how does a PET scanner work?
- small amt of radioactive water injected into subject
- active areas of the brain use more blood, thus have more radioactivity
- positrons from radioactivity are released & collide w/ electrons in the brain, producing photons, which exit the head + are detected
radioactive 15O molecules release tiny positively charged subatomic particles known as ___, which are ___
positrons; electrons w/ a positive charge
how are photons produced for PET scans?
positrons collide w/ electrons in the brain, annihilating them both, producing energy in the form of two photons
explain the subtraction procedure PET researchers use
subtract the blood-flow pattern when the brain is in a controlled state from the pattern of blood flow imaged when the subject is engaged in the task
PET does not measure local neural activity directly; rather, it ___
infers activity on the assumption that blood flow increases where neuron activity increases
significant limitation of PET
radiochemicals must be prepared in a cyclotron quite close to the scanner bc their half-lives are so short that transport time is a severely limiting factor = expensive
3 advantages to PET
- mapping of a wide range of brain changes/conditions, including changes in pH, glucose, oxygen, amino acids, neurotransmitters, + proteins
- can detective relative amounts of a neurotransmitter, the density of neurotransmitter receptors, & metabolic activities associated w/ learning, brain poisoning, + degenerative processes that relate to aging
- used to study cognitive function w/ great success
PET confirms that various brain regions perform ___ functions
different
advantage to hybrid scanners
can acquire high-quality anatomical images, then overlay the functional/metabolic image info, allowing for precise localization - all within a single examination
the simplest way to measure brain chemistry
extract tissue postmortem from affected humans or animals & undertake traditional biochemical techniques, like high-performance liquid chromatography (HPLC)
dopamine levels fluctuate in the ___ in association w/ stimuli related to rewarding behaviours such as food and sex
nucleus accumbens
changes in brain chemistry can be measured in freely moving animals using 2 methods:
- cerebral microdialysis
- cerebral voltammetry
technique used to determine the chemical constituents of extracellular fluid in freely moving animals
microdialysis
how does microdialysis work?
- catheter w/ semipermeable membrane tip is placed in the brain
- fluid flows thru cannula & passes along cell membrane
- simple diffusion drives extracellular molecules across membrane along their concentration gradient
- fluid containing molecules from the brain exits thru tubing to be collected for analysis
microdialysis
caudate nucleus & putamen of the basal ganglia
striatum
if a rat is placed in an environment in which it anticipates sex or favoured food, microdialysis will record an increase in ___ within the striatum
dopamine
physicians use ___ to monitor changes in the brain after TBI or stroke
microdialysis
technique used to identify the concentration of specific chemicals in the brain as animals behave freely
cerebral voltammetry
how does cerebral voltammetry work?
- small carbon fiber electrode + metal electrode implanted in the brain
- weak current passed thru metal electrode
- current causes electrons to be added/removed from surrounding chemicals
- changes in extracellular levels of specific neurotransmitters can be measured as they occur
advantage to voltammetry
not requiring the chemical analysis of fluid removed from the brain
disadvantage to voltemmetry
destructive (degradation of chemicals)
who used voltammetry to demonstrate that the stress hormone corticosterone induced an increase in the amt of dopamine + how long it was detected in the nucleus accumbens?
Wheeler
who’s findings proved that stress can potentiate the effect of reinforcers?
Wheeler
what gene is related to the production of the brain-derived neurotrophic factor (BDNF), which stimulates neural plasticity & low levels indicate mood orders like depression?
BDNF Val 66Met & BDNF Val 66Val
who showed that the Met (BDNF Val 66) allele is associated w/ an 11% reduction in hippocampal volume?
Joshua Bueller
what is the BDNF Vall 66Met allele associated with?
11% reduction in hippocampal volume, poor episodic memory
what is the BDNF Vall 66Val allele associated with?
better episodic memory, higher incidence of neuroticism/anxiety disorders
ADD and ADHD affect ___ of school-aged children
4%-10%
an estimated ___ of children w/ ADHD still show symptoms in adulthood, where its behaviours are associated with ___
50%; family breakups, substance abuse, driving accidents
the neurobiological basis of ADD + ADHD is believed to be a dysfunction in the ___, especially in the ___ circuitry
noradrenergic or dopaminergic activating system; frontal basal ganglia
psychomotor stimulants such as ___ act to increase brain levels of noradrenaline + dopamine are widely used for treating ADHD
ritalin (methylphenidate) & adderall (dextroamphetamine)
about ___ of children show improvement of attention & hyperactive symptoms with treatment, but do not directly improve academic achievement as ___ of children with ADHD fail to get a high-school diploma
70%; 40%
Ritalin works by blocking ___
dopamine reuptake
ADHD is believed to be highly ___, genes relating to the D4 receptor are of particular importance
heritable
who investigated epigenetic patterns in 40 pairs of identical twins supported the findings of less than 100% concordance for diseases?
Mario Fraga
who has shown that the amount of maternal attention mother rats give to their newborns alters the expression of certain genes in the adult hippocampus, indicating these genes are related to the infants’ stress response when they are adults?
Moshe Szyf & Michael Meaney
who examined that epigenetic changes found in the abused suicide victims parallel those found in the rats w/ inattentive mothers, suggesting early experiences can alter hippocampal organization & function via changes in gene expression?
McGowan
who found that stressing pregnant rats led to wide changes in gene expression in their offspring, in both the frontal cortex & hippocampus?
Richelle Mychasiuk
___ in postmortem tissue allows detailed analysis of macro + micro structure; identifying brain pathology (Parkinson) can lead to insights about causes/nature of a disorder
morphology (structure)
2 approaches to research methods
- morphology (structure) in postmortem tissue
- neuron’s electrical activity relating to behaviour or functional changes in brain activity during specific types of cognitive processing
practical issues researchers must consider:
- temporal resolution
- spatial resolution
- degree of invaseiveness
why are MRI-based methods for young children not a good idea?
difficulty remaining absolutely still for long periods of time
___ are noninvasive & relatively inexpensive @ less than $100,000 each
EEG, ERP, fNIRS
___ are very expensive @ over $2 million each, thus only found in research centres or hospitals
MRI-based methods, MEG, PET
the general ___ across mammalian species is remarkably similar, as is the functioning of ___
brain organization; basic neural circuits
2 important issues for using animal models to develop treatments for brain/behavioural disorders
- whether animals actually display neurological diseases in ways similar to humans
- ethics of using animals in research
why is it hard to use animals to model ADHD?
they do not go to school, which is where most problems occur for children
what rat strain is a good model for ADHD?
Kyoto SHR rat
4 principles for reviewing experimental/teaching protocols using animals:
- must promise to contribute to the understanding of principles or development of knowledge that can reasonably be expected to benefit all
- optimal standard for animal health/care result in enhanced credibility/reproducibility of results
- acceptance of animal use depends on maintaining public confidence to ensure necessary, human & justified animal use
- animals used only if there are no alternatives
legislation regarding lab animals in the US is set forth in the ___ which includes laws passed by congress in ___
Animal Welfare Act; 1966, 1970, 1976, 1985
the US Animal Welfare Act includes rats, mice, cats, dogs, primate, and birds but excludes ___
farm animals
companies using animals for research that do not follow the same process as universities are ___ because ___ - so they use Good Laboratory Practice (GLP) standards
unable to publish the results of their research; journals require that research conform to national guidelines on animal care
in the US, the ___ regulates testing of pharmacological and toxic compounds
National Institute of Environmental Health Science
